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BACKGROUND: Children with nephrotic syndrome are exposed to alternate day steroids for prolonged periods and this poses the need for evaluation of adrenocortical suppression using the adrenocorticotropic hormone (ACTH) stimulation test. METHODS: This cross-sectional study enrolled children (2-18 years) both with steroid sensitive nephrotic syndrome (SSNS) (n = 27) and steroid resistant (SRNS) (n = 25); those on daily prednisolone or having serious bacterial infections or hospitalized were excluded. The primary objective was to determine prevalence of adrenocortical suppression in those on low dose alternate day steroids for more than 8 weeks or having received > 2 mg/kg/d for > 2 weeks in the past 1 year and currently in remission. A baseline morning fasting sample of serum cortisol was taken and 25 IU of ACTH (Acton Prolongatum*) injected intramuscularly and repeat serum cortisol sample taken after 1 h. All patients with 1 h post ACTH cortisol < 18.0 µgm/dl were diagnosed with adrenal insufficiency. Receiver operating characteristic curve was drawn to predict the prednisolone dose for adrenal insufficiency. RESULTS: Fifty-two (33 males) children were enrolled (mean age 9.4 years); proportion of adrenal insufficiency was 50% and 64% using baseline and post stimulation cutoffs. The total cumulative annual dose of prednisolone 0.22 mg/kg/day predicted adrenocortical suppression with AUC 0.76 (95% CI 0.63-0.89), with sensitivity of 63.9% and specificity of 81.3%. CONCLUSIONS: A significant proportion of children with nephrotic syndrome were detected with adrenal insufficiency on ACTH stimulation test. A cumulative steroid intake of > 0.22 mg/kg/day on an alternate day basis emerged as a risk factor for predicting adrenocortical suppression.
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Insuficiencia Suprarrenal , Síndrome Nefrótico , Masculino , Niño , Humanos , Síndrome Nefrótico/tratamiento farmacológico , Hidrocortisona , Estudios Transversales , Corticoesteroides/uso terapéutico , Hormona Adrenocorticotrópica , Prednisolona/uso terapéuticoRESUMEN
Background: The urinary biomarker response precedes the appearance of any renal structural or functional derangement. Transforming growth factor-ß1 (TGF-ß1), neutrophil gelatinase associated lipocalin (NGAL), and Cystatin C (CysC) can act as the early prognostic markers in posterior urethral valve (PUV) patients. Aim: To compare the urinary levels of TGF-ß1, NGAL, and CysC between PUV cases and age matched controls and to correlate these with renal structural and functional parameters. Materials and Methods: This prospective study included children with PUV diagnosed using the standard investigations and an equal number of age-matched controls with nonurological problems. For the study subjects, the urinary samples were collected at three different time points (pre- and postoperatively at 3 and 6 months), whereas for controls, only single-voided samples were studied. The urinary levels of TGF-ß1, NGAL, and CysC were estimated by the standardized techniques using the ELISA kits. Statistical methods were used to drive the comparisons between cases and controls. Results: Fifteen children with a median age of 10 (5-48) months were enrolled in each of the two groups. The mean uTGF-ß1 in the case group was significantly higher at all three time points (43.20 ± 6.13 pg/ml, 43.33 ± 11.89 pg/ml and 40.71 ± 9.01 pg/ml) as compared to the control group (29.12 ± 8.31 pg/ml) (P ≤ 0.001). The median uNGAL in the case group was also higher (17.78 ng/ml, 2.35 ng/ml and 2.536 ng/ml) as compared to the control group (1.31 ng/ml). However, the difference was significant only preoperatively (P = 0.02). The median uCysC in case group was similarly higher (0.347 µg/ml, 0.439 µg/ml, and 0.382 µg/ml) than the control group (0.243 µg/ml) (P > 0.05). Serum creatinine in the case group (0.49 mg/dl) showed no significant rise above that of control (0.24 mg/dl). A cutoff value of uTGF-ß1 = 36.55 pg/ml (P < 0.001), uNGAL = 0.879 ng/ml (P = 0.02), and uCysC = 0.25 µg/ml (P = 0.22) was found to be associated with renal damage in PUV. A significant correlation was found between uNGAL and S. creatinine at 3 months (r = 0.43, P = 0.017) and 6 months (r = 0.47, P = 0.08). Conclusion: The elevated uTGF-ß1, a decline in uNGAL and an increase in uCysC suggests ongoing inflammation, improvement in hydronephrosis and a prolonged proximal tubular dysfunction in PUV patients, respectively.
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Post-transcriptional regulation of gene expression plays a major role in determining the cellular proteome in health and disease. Post-transcriptional control mechanisms are disrupted in many cancers, contributing to multiple processes of tumorigenesis. RNA-binding proteins (RBPs), the main post-transcriptional regulators, often show altered expression and activity in cancer cells. Dysregulation of RBPs contributes to many cancer phenotypes, functioning in complex regulatory networks with other cellular players such as non-coding RNAs, signaling mediators and transcription factors to alter the expression of oncogenes and tumor suppressor genes. RBPs often function combinatorially, based on their binding to target sequences/structures on shared mRNA targets, to regulate the expression of cancer-related genes. This gives rise to cooperativity and competition between RBPs in mRNA binding and resultant functional outcomes in post-transcriptional processes such as mRNA splicing, stability, export and translation. Cooperation and competition is also observed in the case of interaction of RBPs and microRNAs with mRNA targets. RNA structural change is a common mechanism mediating the cooperative/competitive interplay between RBPs and between RBPs and microRNAs. RNA modifications, leading to changes in RNA structure, add a new dimension to cooperative/competitive binding of RBPs to mRNAs, further expanding the RBP regulatory landscape. Therefore, cooperative/competitive interplay between RBPs is a major determinant of the RBP interactome and post-transcriptional regulation of gene expression in cancer cells.
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MicroARNs , Neoplasias , Humanos , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , ARN Mensajero/genética , ARN Mensajero/química , ARN Mensajero/metabolismo , MicroARNs/genética , Regulación de la Expresión Génica , Neoplasias/genética , Neoplasias/patología , Factores de Transcripción/genéticaRESUMEN
Quorum-sensing mechanisms that sense the density of immune cells at the site of inflammation to initiate inflammation resolution have recently been demonstrated as a major determinant of the inflammatory response. We observed a density-dependent increase in expression of the inflammatory tumor suppressor protein programmed cell death 4 (PDCD4) in mouse macrophage cells. Conditioned medium from high-density cells upregulated PDCD4 expression, revealing the presence of a secreted factor(s) acting as a macrophage quorum sensor. Secreted gelsolin (GSN) was identified as the quorum-sensing autoinducer. Alteration of GSN levels changed PDCD4 expression and the density-dependent phenotype of cells. LPS induced the expression of microRNA miR-21, which downregulated both GSN and PDCD4 expression, and reversed the high-density phenotype. The high-density phenotype was correlated with an anti-inflammatory gene expression program, which was counteracted by inflammatory stimulus. Together, our observations establish the miR-21-GSN-PDCD4 regulatory network as a crucial mediator of a macrophage quorum-sensing mechanism for the control of inflammatory responses.
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Gelsolina , MicroARNs , Animales , Apoptosis , Gelsolina/genética , Gelsolina/metabolismo , Macrófagos/metabolismo , Ratones , MicroARNs/genética , Fenotipo , Percepción de QuorumRESUMEN
Aim: The aim is to compare the diagnostic accuracy of laboratory investigations and ultrasonography (USG) in distinguishing complicated appendicitis (C-AA) from uncomplicated appendicitis (UC-AA). Materials and Methods: Forty-six children who underwent appendicectomy at our center between November 2018 and July 2020 were included. Based on intraoperative findings, they were divided into two groups - complicated (perforated, gangrenous, or associated with fecal peritonitis; n = 18) and UC-AA (n = 28). USG findings and inflammatory markers were compared in both groups at admission. Results: At admission, the mean values for total leukocyte count (TLC) (16090.56 vs. 11739.29 per mm3), high sensitivity C-reactive protein (hsCRP) (35.8 vs. 31.62 mg/L), and procalcitonin (PCT) (3.83 vs. 1.41 ng/mL) were significantly higher in C-AA. Visualization of a blind tubular aperistaltic structure was the only sonographic sign showing statistical significance - significantly lower in C-AA (50% vs. 90%). Independent predictors of C-AA were - duration of symptoms >48 h (odds ratio [OR] 6.3), free fluid/loculated collection in right iliac fossa (OR 3.75), TLC >11000/mm3 (OR 3.6), hsCRP >35 mg/L (OR 6.0), PCT >0.6 ng/mL (OR 4.02), and nonvisualization of appendix on USG (OR 8.33). Biochemical factors were sensitive (89%) and specific (55%) in differentiating C-AA from UC-AA but the addition of sonological parameters significantly improved the specificity of predicting complicated AA to 61% (P = 0.0036). Conclusion: Combining laboratory data with sonological findings significantly improves the predictive value for differentiating C-AA from UC-AA and can help decide operative approach and prognosticating.
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The present study was conducted from July 1, 2020 to September 25, 2020 in a dedicated coronavirus disease 2019 (COVID-19) hospital in Delhi, India to provide evidence for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in atmospheric air and surfaces of the hospital wards. Swabs from hospital surfaces (patient's bed, ward floor, and nursing stations area) and suspended particulate matter in ambient air were collected by a portable air sampler from the medicine ward, intensive care unit, and emergency ward admitting COVID-19 patients. By performing reverse-transcriptase polymerase chain reaction (RT-PCR) for E-gene and RdRp gene, SARS-CoV-2 virus was detected from hospital surfaces and particulate matters from the ambient air of various wards collected at 1 and 3-m distance from active COVID-19 patients. The presence of the virus in the air beyond a 1-m distance from the patients and surfaces of the hospital indicates that the SARS-CoV-2 virus has the potential to be transmitted by airborne and surface routes from COVID-19 patients to health-care workers working in COVID-19 dedicated hospital. This warrants that precautions against airborne and surface transmission of COVID-19 in the community should be taken when markets, industries, educational institutions, and so on, reopen for normal activities.
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Prueba de Ácido Nucleico para COVID-19/métodos , COVID-19/epidemiología , COVID-19/transmisión , Fómites/virología , ARN Viral/genética , SARS-CoV-2/genética , Aire/análisis , COVID-19/prevención & control , Proteínas de la Envoltura de Coronavirus/genética , ARN Polimerasa Dependiente de ARN de Coronavirus/genética , Hospitales , Humanos , India/epidemiología , Unidades de Cuidados Intensivos , Material Particulado/análisisRESUMEN
Background As breast epithelium is affected by vitamin D, it may have a direct effect on breast density and the risk of breast cancer. Our aim was to study the serum levels of vitamin D in patients with malignant and benign breast disease, and to study the association, if any, between vitamin D levels, mammographic breast density (MD) and molecular subtypes of breast cancer. Methods In this cross-sectional, observational study, we enrolled 162 consecutive adult women with benign and malignant breast masses subjected to mammography and core-needle biopsy. Serum levels of vitamin D were estimated and correlated with MD and with immunohistochemical subtyping of breast cancer. Results The mean vitamin D level in these 162 patients was 12.44 (5.88) ng/ml, with vitamin D deficiency seen in 98%. The mean (SD) vitamin D level in MD type 1 was 16.19 (4.62) ng/ml and it decreased to 7.54 (2.58) ng/ml in MD type 4. High MD was associated with significantly lower vitamin D levels. The mean vitamin D level in patients with benign breast disease (n=102) was 13.73 (5.68) ng/ml, while it was significantly lower in patients with breast cancer (n=60) at 10.26 (5.61) ng/ml. Among patients with breast cancer, the good prognosis luminal A molecular subtype had mean vitamin D level of 12.94 (6.16) ng/ml, whereas the poor prognosis triple-negative subtype had a significantly lower value of 7.68 (3.42) ng/ml. Conclusion Our study shows that vitamin D deficiency has a significant relationship with breast cancer (v. benign breast disease), high MD (showing increased breast cancer risk) and poor prognosis triple-negative breast cancer. Vitamin D deficiency could be an important, potentially modifiable, risk factor for the prevention of breast cancer in susceptible populations.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Deficiencia de Vitamina D , Adulto , Densidad de la Mama , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , Estudios Transversales , Femenino , Humanos , Neoplasias de la Mama Triple Negativas/complicaciones , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen , Neoplasias de la Mama Triple Negativas/epidemiología , Vitamina D , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiologíaRESUMEN
BACKGROUND: Oral squamous cell carcinoma (OSCC) is a cancer of the oral cavity that is a major health problem in India. There is an urgent need to identify biomarkers that have prognostic significance. We studied HIF-1α levels as well as single-nucleotide polymorphism of HIF-1α gene in cancer and healthy controls. METHODS: Fifty newly diagnosed OSCC patients and 50 age and sex-matched healthy control were included in the study. Serum concentrations of HIF-1α were measured by sandwich ELISA; whereas HIF-1α gene polymorphism study was performed using restriction enzyme digestion by HpH I. RESULTS: The major genotype observed was CC genotype in both control (84%) and patients (86%) followed by CT genotype (control 16%, cases 14%). CT genotype led to more aggressive tumors. On subgroup analysis based on prognosis, the median overall survival of patients who were treatment responders was 488 days (16.2 months) and that of the patients with progressive disease was 365 days (12.1 months). The patients who expired during the study observation period had median survival of 330 days (11 months). CONCLUSION: Our study showed that CT genotype for C1772T polymorphism of HIF-1α predisposes to aggressive tumor phenotype in patients with OSCC. Moreover, patients with CT genotype had poor survival rate as compared to CC genotype. A cut-off value of 460 pg/mL of HIF-1α can help to segregate patients with OSCC from healthy controls.
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Biomarcadores de Tumor/genética , Estudios de Asociación Genética , Genotipo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Neoplasias de la Boca/genética , Polimorfismo Genético/genética , Biomarcadores de Tumor/sangre , Femenino , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/sangre , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/mortalidad , Valor Predictivo de las Pruebas , Pronóstico , Tasa de Supervivencia , Factores de TiempoRESUMEN
Polycystic ovary syndrome (PCOS) is a common endocrinological disorder among women of the reproductive age group with long term sequelae which include diabetes mellitus, hypertension and CAD. The present study was conducted to evaluate the association of leptin-an adipokine playing an important role in carbohydrate metabolism and markers of insulin resistance among women with PCOS. Sixty diagnosed cases of PCOS as per Rotterdam criteria were enrolled in this study after informed written consent. Insulin resistance was estimated using the homeostatic model assessment-insulin resistance (HOMA-IR). HOMA-IR was calculated as the product of the fasting plasma insulin value (mU/ml) and the fasting plasma glucose value (mg/dl), divided by 405 and HOMA ß was calculated as 360 × [insulin]/([glucose] - 63) % (glucose in mg/dl). Estimation of serum leptin levels was done by ELISA using leptin ELISA kit from (DRG). A positive correlation of serum leptin levels was observed with markers of insulin resistance. Multiple regression analysis with HOMA-IR as dependent variable demonstrated a statistically significant contribution of fasting insulin levels. This study highlights the role of leptin in alterations in carbohydrate metabolism in patients with PCOS.
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Coronary artery disease (CAD) is a global epidemic currently. This study was planned to evaluate markers of inflammation and hemostasis and their possible association, if any, in patients with CAD. The study was carried out in 60 patients with acute myocardial infarction (AMI) and 60 age and gender matched controls. The following parameters were assayed in all study subjects-inflammatory-interleukin (IL)-10, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, fibrinogen; hemostatic-fibrinogen, fibrin D-dimer and a novel risk factor-homocysteine. Inflammatory markers (hs-CRP, TNF-α and IL-10), fibrinogen, fibrin D-dimer and homocysteine levels were significantly higher in the patients with AMI, as compared with controls. A positive correlation was observed between D-dimer and the inflammatory markers-hs-CRP and TNF-α. Upon multivariate analysis, TNF-α emerged as the best determinant of CAD in our study. Our results indicate that there is a possible interplay of inflammation and hemostasis in CAD, underlining their synergistic role in the pathogenesis of CAD.
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Low back pain is very disabling and dispiriting because of the physical impediment it causes and its psychological effects. Innumerable factors have been implicated in its etiology. In spite of improvements in diagnostic modalities, a considerable number of such cases fall in the ambiguous zone of unknown etiology or 'idiopathic.'Early diagnosis of low back pain will allow effective prevention and treatment to be offered. This study was conducted to assess the contribution of vitamin D levels and other biochemical factors to chronic low back pain in such cases. All patients attending the orthopedics OPD for low back pain in whom a precise anatomical cause could not be localized, were prospectively enrolled in this study. We measured serum levels of glucose, calcium, phosphorus, uric acid, rheumatoid factor, C reactive protein, alkaline phosphatase, total protein, albumin and 25 (OH) D concentrations in 200 cases and 200 control samples. The patients showed significantly lower vitamin D levels compared to controls with p value < 0.0001. The maximum number of low back pain patients were in the age group of 31-50 years (42 %).The average BMI was 23.27 ± 5.17 kg/sq m, 73 % of total patient population were females and 27 % were known case of type 2 diabetes mellitus. Calcium, alkaline phosphatase, was positively correlated with vitamin D and glucose showed a negative correlation with vitamin D in the patient population. The problem of low back pain provides a challenge to health care providers. The problem in developing countries is compounded by ignorance to report for early treatment and occupational compulsions in rural areas and sedentary lifestyle in urban youth. The authors strongly recommend early frequent screening for vitamin D along with glucose, protein, albumin, calcium, phosphorus, CRP as part of general health checkup for non-specific body pain, especially low back pain.
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Preeclampsia is a multisystem disorder associated with maternal hypertension, placental abnormalities and adverse fetal outcomes. The various pathways involved in its etiology include endothelial dysfunction, inflammatory milieu, lipid peroxidation and immunological imbalance. The present study was conducted to evaluate the causative and predictive role of nitric oxide, lipid peroxidation end products (MDA) and inflammatory cytokines (IL-6, TNF-α) in clinical presentation, severity and fetal outcome in preeclampsia. The study population was divided into 3 groups- Non- pregnant females comprising the control population; G1 and G2 groups included normal pregnant and pregnant females with preeclampsia with 50 patients in each group. Nitric Oxide and MDA levels were found to be highest in the preeclamptic patients as compared to other two groups. ROC curve analysis shows the superiority of the inflammatory markers as determinants of severity of preeclampsia which suggests the emerging role of pro inflammatory markers in the various pathological changes in preeclampsia. TNF-α emerged as the best marker in multivariate analysis and thus, has the potential for being used as a marker for PIH. Our study illustrates the multifactorial etiology of preeclampsia involving oxidative stress, proinflammatory milieu and endothelial dysfunction.
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D-dimer, a universally unique marker for fibrin degradation, is generated through the enzymatic interplay of thrombin, factor XIIIa, and plasmin. The emergence of D-dimer-containing fibrin molecules occurs in both intravascular and extravascular spaces during pivotal physiological processes like haemostasis, thrombosis, and tissue repair. Given the inherently physiological nature of fibrin formation and fibrinolysis, basal levels of D-dimer fragments are present in plasma. Beyond its role as a marker of routine physiological processes, aberrations in D-dimer levels are indicative of a spectrum of conditions, both non-pathological and pathological. The clinical utility of D-dimer has been firmly established, particularly in scenarios like venous thromboembolism (VTE), pulmonary embolism (PE), deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC). Additionally, recent applications have extended to assess the prognosis of COVID-19. While D-dimer is commonly associated with thrombotic conditions, its elevation is not confined to these conditions alone. Elevated D-dimer levels are observed across various diseases, where its significance extends beyond diagnostic indicators to prognostic implications.
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Biomarcadores , COVID-19 , Productos de Degradación de Fibrina-Fibrinógeno , Humanos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , COVID-19/sangre , COVID-19/diagnóstico , Biomarcadores/sangre , SARS-CoV-2 , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/sangre , Fibrinólisis , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/sangre , Pronóstico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/sangre , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/sangreRESUMEN
Medical science is a dynamic field of knowledge that is constantly broadening with upcoming clinical research and analysis. Traditional medical education has been focused on textbook-based recall assessments-closed book assessment (CBA). However, the availability of newer technologies has made the accessibility to encyclopedic knowledge expeditious, which demands for a new approach for medical education. As medical professionals, the purpose of learning should be higher cognitive skills such as interpretation and synthesis. So, analyzing students' ability to comprehend the concepts and learning to apply it in a realistic context than merely recalling the facts has come into attention. In this study, we aimed to evaluate and compare the performance of 250 first-year MBBS students at Maulana Azad Medical College, New Delhi, India, between closed book and open book method for biochemistry. Students were divided into two groups, Group A and Group B, based on their average monthly internal assessment marks. CBA was followed by open book assessment (OBA) 1 week apart with similar questionnaire pattern and allotted time. A significant difference in average marks obtained by the two groups was observed in CBA. Group A scored better in CBA, but performance was comparable with Group B in OBA. OBA and CBA can contribute to an assessment program in part because of their complementary pros and cons, and OBA should not be thought of as an alternative to CBA, but their value may be in expanding beyond what is measured by CBA.
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Educación de Pregrado en Medicina , Evaluación Educacional , Estudiantes de Medicina , Humanos , Evaluación Educacional/métodos , Educación de Pregrado en Medicina/métodos , Libros , Encuestas y Cuestionarios , India , Bioquímica/educación , MasculinoRESUMEN
Objective: To estimate the proportion and risk factors of non-thyroidal illness (NTI) in children with congenital heart disease (CHD) with congestive heart failure (CHF). Methods: This study enrolled children (6 weeks to 60 months age) with CHD and CHF. The clinical profile and disease severity, derived from the Pediatric Early Warning Score (PEWS) was recorded. Baseline blood samples were taken within 24 hours of hospitalization and evaluated for free tri-iodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), N-terminal pro-brain natriuretic peptide (NT pro-BNP) and reverse T3. Results: A total of 80 (64 acyanotic CHD) children of median (interquartile range) age 5 (2.5, 8.0) months were enrolled. NTI was seen in 37 (46%) of whom 27 had low fT3 levels. The proportion of NTI was highest in children with severe disease (20/30), than moderate (4/9) or mild disease (13/41) (p=0.018). Ten (27%) patients with NTI died compared to 2 (4.7%) without NTI with unadjusted odds ratio (OR) [95% confidence interval (CI)] 7.593 (1.54, 37.38); p=0.006. After adjusting for NTI, shock and NT-pro-BNP levels, PEWS was the only significant predictor of mortality (OR: 1.41, 95% CI: 1.03, 1.92; p=0.032). Linear regression for fT3 identified a significant relationship with log NT-BNP [beta -3.541, (95% CI: -1.387, -0.388)] and with TSH [beta 2.652 (95% CI: 0.054, 0.383)]. The cutoff (area under the curve, 95% CI) that predicted mortality were fT4 <14.5 pmol/L (0.737, 0.60, 0.88), fT3/rT3 index <1.86 pg/ng (0.284, 0.129, 0.438) and NT pro-BNP >3725 pg/mL (0.702; 0.53, 0.88). Conclusion: NTI was present in a significant proportion of children with CHD and CHF. fT3 level was significantly associated with NTBNP levels and thus severity of CHF.
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Insuficiencia Cardíaca , Índice de Severidad de la Enfermedad , Humanos , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/diagnóstico , Femenino , Masculino , Preescolar , Lactante , Cardiopatías Congénitas/sangre , Cardiopatías Congénitas/complicaciones , Factores de Riesgo , Péptido Natriurético Encefálico/sangre , Síndromes del Eutiroideo Enfermo/sangre , Síndromes del Eutiroideo Enfermo/epidemiología , Síndromes del Eutiroideo Enfermo/diagnóstico , Fragmentos de Péptidos/sangre , Tiroxina/sangre , Triyodotironina/sangre , Tirotropina/sangre , Biomarcadores/sangre , PronósticoRESUMEN
BACKGROUND: Post-coronavirus disease 2019 (COVID-19) symptoms were widely reported. However, data on post-COVID-19 conditions following infection with the Omicron variant remained scarce. This prospective study was conducted to understand the prevalence, patterns, and duration of symptoms in patients who had recovered from COVID-19. METHODS: A prospective study was conducted across 11 districts of Delhi, India, among individuals who had recovered from COVID-19. Study participants were enrolled, and then returned for post-recovery follow-up at 3 months and 6 months interval. RESULTS: The mean age of study participants was 42.07 years, with a standard deviation of 14.89 years. The majority of the participants (79.7%) reported experiencing post-COVID-19 symptoms. The most common symptoms included joint pain (36.0%), persistent dry cough (35.7%), anxiety (28.4%), and shortness of breath (27.1%). Other symptoms were persistent fatigue (21.6%), persistent headache (20.0%), forgetfulness (19.7%), and limb weakness (18.6%). The longest duration of symptom was observed to be anxiety (138.75±54.14 days), followed by fatigue (137.57±48.33 days), shortness of breath (131.89±60.21 days), and joint pain/swelling (131.59±58.76 days). At the first follow-up visit, 2.2% of participants presented with abnormal electrocardiogram readings, but no abnormalities were noticed during the second follow-up. Additionally, 4.06% of participants exhibited abnormal chest X-ray findings at the first followup, which decreased to 2.16% by the second visit. CONCLUSION: The most frequently reported post-COVID-19 symptoms were joint pain, dry cough, anxiety and shortness of breath. These clinical symptoms persisted for up to 6 months, with evidence of multi-system involvement. Consequently, findings highlighted the need for long-term follow-up during the post-COVID-19 period.
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BACKGROUND: A guanine/cytosine (G/C) substitution occurring in position -174 of the interleukin-6 (IL-6) gene promoter changes the expression of IL-6 circulating proteins. We evaluated the occurrence of IL-6 -174 G/C polymorphism in patients with acute ischemic stroke and studied its association with stroke severity, outcome, and mortality. METHODS: One hundred patients with acute ischemic stroke and 120 age and sex-matched healthy controls were studied. Genotyping was performed using polymerase chain reaction and restriction enzyme analysis. Serum levels of IL-6 were measured using enzyme-linked immunosorbent assay. Stroke was classified using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Severity was assessed by the National Institutes of Health Stroke Scale. Outcome measures included modified Rankin Scale (mRS) and Barthel Index (BI) scores at 7 days and 3 and 6 months. Mortality/survival was assessed using the Kaplan-Meier analysis. RESULTS: The frequency of GG, GC, and CC genotypes did not differ significantly between cases and controls. No association was seen between TOAST subtype and genotype. At the time of admission, stroke was more severe in patients with the GC genotype (P = .03) and less severe in the GG genotype (P = .04). The GC genotype was also associated with higher serum IL-6 levels and poor short-term (BI P = .001; mRS P = .003) and long-term outcomes (BI P = 9 × 10(-5); mRS P = 9 × 10(-5)), while the GG genotype had significantly lower serum IL-6 levels and better short and long-term outcomes (BI P = 3 × 10(-5); mRS P = 2 × 10(-4)). There was significantly lesser mortality in the GG genotype and more in the GC genotype based on the Kaplan-Meier analysis. CONCLUSIONS: Patients with the GC genotype had more severe strokes with poorer short and long-term outcomes and increased mortality. The GG genotype was associated with less severe strokes, better short and long-term prognosis, and survival. The GG genotype appears to be protective against stroke severity, outcome, and mortality.
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Isquemia Encefálica/genética , Interleucina-6/genética , Polimorfismo Genético , Regiones Promotoras Genéticas , Accidente Cerebrovascular/genética , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etnología , Isquemia Encefálica/inmunología , Isquemia Encefálica/mortalidad , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Evaluación de la Discapacidad , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , India/epidemiología , Interleucina-6/sangre , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etnología , Accidente Cerebrovascular/inmunología , Accidente Cerebrovascular/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Inflammation plays a crucial role in the pathogenesis and prognosis of stroke. We studied the behavior of lipoprotein(a) [Lp(a)], ferritin, and albumin as acute phase reactants and their roles in the severity and mortality of stroke. METHODS: We recruited 100 consecutive patients with acute ischemic stroke and 120 controls. Blood samples were drawn on days 1 and 7 and at both 3 and 6 months. Stroke was classified using Trial of Org 10172 in Acute Stroke Treatment classification. Stroke severity was assessed using the National Institutes of Health Stroke Scale. Prognosis at 6 months was assessed using the modified Rankin Scale, and mortality was assessed using the Kaplan-Meier analysis. Serum levels of interleukin-6 (IL-6), Lp(a), ferritin, and albumin were measured using enzyme-linked immunosorbent assay, immunoturbidimetry, and chemiluminescence commercial kits, respectively. RESULTS: Levels of IL-6, Lp(a), and ferritin were consistently higher among cases than controls (P < .0001). Serum Lp(a) levels peaked at day 7 after stroke and tapered thereafter. Albumin levels were lower than controls on admission day and increased subsequently. In our study, Lp(a) acted as an acute phase reactant while albumin acted as a negative acute phase reactant. There was no association between Trial of Org 10172 in Acute Stroke Treatment subtype and elevated serum levels of Lp(a), albumin, and ferritin. Lp(a) and ferritin were high in patients with severe stroke. Albumin was negatively correlated with stroke severity. Serum levels of Lp(a) ≥ 77 mg/dL, albumin ≤ 3.5 g/dL, and ferritin ≥ 370 ng/dL is associated with a significantly increased risk of having a poorer outcome in stroke. Serum levels of Lp(a) >77 mg/dL and albumin <3.5 g/dL were also associated with increased mortality. CONCLUSIONS: High levels of Lp(a) and ferritin and low levels of albumin are associated with increased severity and poorer long term prognosis of stroke. Patients with admission levels of Lp(a) >77 mg/dL and albumin <3.5 g/dL had increased mortality.
Asunto(s)
Reacción de Fase Aguda/mortalidad , Isquemia Encefálica/mortalidad , Ferritinas/sangre , Lipoproteína(a)/sangre , Accidente Cerebrovascular/mortalidad , Reacción de Fase Aguda/sangre , Reacción de Fase Aguda/etiología , Anciano , Isquemia Encefálica/sangre , Isquemia Encefálica/complicaciones , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Pronóstico , Albúmina Sérica , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/complicacionesRESUMEN
Inflammatory pathways have garnered considerable interest in the recent past as an important mediator of the molecular mechanisms leading to carcinogenesis. The present study was conducted to evaluate the correlation of levels of IL-6 with tumor burden and receptor status in patients of locally advanced carcinoma breast. This prospective study was conducted by the collaborative efforts of the departments of Surgery and Biochemistry, Maulana Azad Medical College and associated Lok Nayak Hospital and GB Pant Hospitals, New Delhi. The study population comprised of 30 cases of locally advanced breast carcinoma recruited from the surgical outpatient department. The various parameters that were evaluated include detailed clinico-pathological profile and IL-6 levels. Tissue specimens received after surgeries were examined for the various characteristics indicative of tumor prognosis. Majority of the patients was in the age group of 41-50 years and was postmenopausal. The serum level of IL-6 increased as the disease progressed from T3N1M0 to T4dN2M0 (41.4 ± 31.9 vs. 164.0 ± 31.1 pg/ml respectively). There was significant correlation of IL-6 levels with lymph node involvement, tumor grade, mitotic index and adipose tissue invasion. Emerging molecular markers are being investigated for breast cancer prognosis assessment and prediction of response to chemotherapy including selection of best possible treatment modality. Our study showed that there is progressive increase in IL-6 levels as the stage of disease progresses.
RESUMEN
Post-transcriptional regulation of p53, by the microRNA miR-125b and the RNA-binding protein HuR, controls p53 expression under genotoxic stress. p53 mRNA translation is repressed by miR-125b, tightly regulating its basal level of expression. The repression is relieved upon DNA damage by a decrease in miR-125b level, contributing to pulsatile expression of p53. The pulse of p53, as also of HuR, in response to UV irradiation coincides with a time-dependent biphasic change in miR-125b level. We show that the cause for the decrease in miR-125b level immediately post DNA-damage is enhanced exosomal export mediated by HuR. The subsequent increase in miR-125b level is due to p53-mediated transcriptional upregulation and enhanced processing, demonstrating miR-125b as a transcriptional and processing target of p53. p53 activates the transcription of primary miR-125b RNA from a cryptic promoter in response to UV irradiation. Together, these regulatory processes constitute reciprocal feedback loops that determine the biphasic change in miR-125b level, ultimately contributing to the fine-tuned temporal regulation of p53 expression in response to genotoxic stress.